磷酸二酯酶4在心脏疾病中作用的研究进展

Progress in role of phosphodiesterase 4 in heart diseases

磷酸二酯酶4(PDE4)是细胞内特异性cAMP水解酶,PDE4可以通过调节心肌细胞内的cAMP水平,进而影响cAMP参与的一系列生理功能的调节。目前,PDE4在慢性阻塞性肺病和银屑癣等疾病中作用的研究较为广泛,该综述旨在介绍PDE4在实验动物和人心肌肥大、心衰和心律失常中作用的研究进展。首先,通过观察大鼠心肌肥大模型发现PDE4水平有明显降低,进而对人类病变的心脏进行研究,表明患病的心脏上PDE4A和PDE4D水解活性也有明显下降;其次,在人心衰的心肌细胞上,存在于心脏兰诺定2型受体/Ca2+复合体中的PDE4D3,水解cAMP的活性也有显著降低;最后,在β肾上腺素刺激下,离体人心肌细胞中PDE4受到抑制后,细胞内cAMP水平和L型Ca2+电流均增加,表明PDE4受抑制会增加心率失常的发生率。

Phosphodiesterase 4 （PDE4） is one of the main enzymes which are specific for the hydrolysis of cAMP. Meanwhile, PDE4 modulates cAMP level in cardiomyocytes, and then impacts on the regulation of a series of physiological functions. At present, the research on PDE4 is relatively wide in chronic obstructive pulmonary disease （COPD） and psoriasis, and this review aims to introduce research progress of the PDE4 in experimental animals and human myocardial hypertrophy, heart failure and arrhythmia. Firstly, by observing the myocardial hypertrophy in rats model, decrease was occurred in PDE4 level. Further, the pathological study of human heart showed that hydrolysis activities of PDE4A and PDE4D have obviously declined.Secondly, in the cardiac muscle cells of human heart failure, the activity of PDE4D3 obtained in the RyR2/Ca2＋ complex was significantly reduced. Finally, with β-adrenergic stimulating, PDE4 was inhibited which resulted in the increase in intracellular cAMP levels and L-type Ca2＋ current in human atrial myocyte. The study indicated that PDE4 inhibition will increase the incidence of arrhythmia.